Introduction To find out the differences in gene characteristics between patients with positive and negative cervical cancer lymph nodes, and to provide a reference for predicting lymph node metastasis of cervical cancer.

Methods From January 2018 to June 2022, 112 cases of cervical cancer underwent genetic testing of 1021 cancer-related genes by next – generation sequencing were analyzed. Patients were grouped according to positive and negative lymph nodes, maftools software was used to analyze the somatic single nucleotide variation/insertion-deletion variation mutation frequency, mutation coexistence and mutual exclusion, cosmic mutation characteristics, and oncogenic signaling pathways in the two groups.

Results The five genes with the highest frequency of somatic SNV/Indel mutations are: PIK3CA (39%), MLL3 (26%), MLL2 (21%), EP300 (15%), and FBXW7 (13%). Further differential analysis find EP300 and FBXW7 are significantly enriched in lymph node-positive patients. Mutation coexistence-mutual exclusion analysis find both lymph node-positive and negative patients have large number of coexisting mutations, while mutually exclusive mutations are rare, and the patterns of coexisting mutations are different between the two groups.Cosmic mutational signature analysis reveal the homologous recombination-mediated DNA repair defect signature is enriched in lymph node-positive, but not in negative patients.

Conclusion/Implications The gene mutation characteristics of both are different, the somatic SNV/Indels of EP300 and FBXW7 are significantly enriched in lymph node positive patients. The co-occurrence and cosmic features of gene mutations are also different, homologous recombination-mediated DNA repair defects only exist in lymph node-positive patients. These different features may be potential molecular markers to predict lymph node metastasis in cervical cancer.